Bench-to-bedside review : targeting antioxidants to mitochondria in sepsis

Peer reviewedPublisher PD

Ideal and actual involvement of community pharmacists in health promotion and prevention: a cross-sectional study in Quebec, Canada

<p>Abstract</p> <p>Background</p> <p>An increased interest is observed in broadening community pharmacists' role in public health. To date, little information has been gathered in Canada on community pharmacists' perceptions of their role in health promotion and prevention; however, such data are essential to the development of public-health programs in community pharmacy. A cross-sectional study was therefore conducted to explore the perceptions of community pharmacists in urban and semi-urban areas regarding their ideal and actual levels of involvement in providing health-promotion and prevention services and the barriers to such involvement.</p> <p>Methods</p> <p>Using a five-step modified Dillman's tailored design method, a questionnaire with 28 multiple-choice or open-ended questions (11 pages plus a cover letter) was mailed to a random sample of 1,250 pharmacists out of 1,887 community pharmacists practicing in Montreal (Quebec, Canada) and surrounding areas. It included questions on pharmacists' ideal level of involvement in providing health-promotion and preventive services; which services were actually offered in their pharmacy, the employees involved, the frequency, and duration of the services; the barriers to the provision of these services in community pharmacy; their opinion regarding the most appropriate health professionals to provide them; and the characteristics of pharmacists, pharmacies and their clientele.</p> <p>Results</p> <p>In all, 571 out of 1,234 (46.3%) eligible community pharmacists completed and returned the questionnaire. Most believed they should be very involved in health promotion and prevention, particularly in smoking cessation (84.3%); screening for hypertension (81.8%), diabetes (76.0%) and dyslipidemia (56.9%); and sexual health (61.7% to 89.1%); however, fewer respondents reported actually being very involved in providing such services (5.7% [lifestyle, including smoking cessation], 44.5%, 34.8%, 6.5% and 19.3%, respectively). The main barriers to the provision of these services in current practice were lack of: time (86.1%), coordination with other health care professionals (61.1%), staff or resources (57.2%), financial compensation (50.8%), and clinical tools (45.5%).</p> <p>Conclusions</p> <p>Although community pharmacists think they should play a significant role in health promotion and prevention, they recognize a wide gap between their ideal and actual levels of involvement. The efficient integration of primary-care pharmacists and pharmacies into public health cannot be envisioned without addressing important organizational barriers.</p

Arp2/3 complex interactions and actin network turnover in lamellipodia

Cell migration is initiated by lamellipodia—membrane-enclosed sheets of cytoplasm containing densely packed actin filament networks. Although the molecular details of network turnover remain obscure, recent work points towards key roles in filament nucleation for Arp2/3 complex and its activator WAVE complex. Here, we combine fluorescence recovery after photobleaching (FRAP) of different lamellipodial components with a new method of data analysis to shed light on the dynamics of actin assembly/disassembly. We show that Arp2/3 complex is incorporated into the network exclusively at the lamellipodium tip, like actin, at sites coincident with WAVE complex accumulation. Capping protein likewise showed a turnover similar to actin and Arp2/3 complex, but was confined to the tip. In contrast, cortactin—another prominent Arp2/3 complex regulator—and ADF/cofilin—previously implicated in driving both filament nucleation and disassembly—were rapidly exchanged throughout the lamellipodium. These results suggest that Arp2/3- and WAVE complex-driven actin filament nucleation at the lamellipodium tip is uncoupled from the activities of both cortactin and cofilin. Network turnover is additionally regulated by the spatially segregated activities of capping protein at the tip and cofilin throughout the mesh

Comparative Dynamics of Retrograde Actin Flow and Focal Adhesions: Formation of Nascent Adhesions Triggers Transition from Fast to Slow Flow

Dynamic actin network at the leading edge of the cell is linked to the extracellular matrix through focal adhesions (FAs), and at the same time it undergoes retrograde flow with different dynamics in two distinct zones: the lamellipodium (peripheral zone of fast flow), and the lamellum (zone of slow flow located between the lamellipodium and the cell body). Cell migration involves expansion of both the lamellipodium and the lamellum, as well as formation of new FAs, but it is largely unknown how the position of the boundary between the two flow zones is defined, and how FAs and actin flow mutually influence each other. We investigated dynamic relationship between focal adhesions and the boundary between the two flow zones in spreading cells. Nascent FAs first appeared in the lamellipodium. Within seconds after the formation of new FAs, the rate of actin flow decreased locally, and the lamellipodium/lamellum boundary advanced towards the new FAs. Blocking fast actin flow with cytochalasin D resulted in rapid dissolution of nascent FAs. In the absence of FAs (spreading on poly-L-lysine-coated surfaces) retrograde flow was uniform and the velocity transition was not observed. We conclude that formation of FAs depends on actin dynamics, and in its turn, affects the dynamics of actin flow by triggering transition from fast to slow flow. Extension of the cell edge thus proceeds through a cycle of lamellipodium protrusion, formation of new FAs, advance of the lamellum, and protrusion of the lamellipodium from the new base

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference